WO2005/080316 (in the name of University College London) discloses compounds capable of modulating cannabinoid or cannabinoid-like receptors, including VSN-16, the structure of which is shown below.

Initial studies demonstrated that VSN-16 and related compounds exhibited a marked effect on spasticity in CREAE mice, providing strong evidence that a selective inhibition of spasticity was achieved without producing significant adverse CNS effects. Studies also demonstrated that the compounds inhibited gastrointestinal motility, as measured using a colonic propulsion test. More recent pharmacological studies have established that VSN-16 and related compounds appear to act on a putative novel cannabinoid receptor of the vasculature (P. M. Hoi, C. Visintin, M. Okuyama, S. M. Gardiner, T. Bennett, D. Baker, D. L. Selwood and C. R. Hiley; British Journal of Pharmacology, 2007, 1-14). VSN-16 is understood to act on the endothelium to release nitric oxide and activate KCa and TRPV1. Its solubility is believed to play a significant role in bringing about peripheral cannabinoid-like effects without accompanying central or severe cardiovascular responses.
WO2005/080316 discloses the preparation of VSN-16 as shown in Scheme 1 below.

In brief, a palladium catalysed Songashira coupling reaction was used to insert a variety of alkyl side chains into 3-iodo methyl benzoate. The target compounds (S5) and related analogues were synthesised by a simple four-step route. First, the acid (S1) was reacted with DL alaminol in the presence of a diimide (EDCI) to give the amide (S2) in good yield. Palladium-catalysed coupling [Hoye, R. C. et al, J. Org. Chem. 1999, 64, 2450-2453; Hopper, A. T. et al, J. Med. Chem. 1998, 41, 420-427] of the amide with the alkyne acid in the presence of CuII and pyrrolidine proceeded smoothly to give the alkyne (S3). The acid (S3) was quantitatively transformed into (S4) using ethylchloroformate and dimethylamine HCl. Lindlar catalysed reduction yielded the target alkene (S5). Alternatively, (S4) can be reduced with borohydride (polymer supported), (CH3COO)2Ni.4H2O, MeOH, and H2 at atmospheric pressure (P. M. Hoi, C. Visintin, M. Okuyama, S. M. Gardiner, T. Bennett, D. Baker, D. L. Selwood and C. R. Hiley; British Journal of Pharmacology, 2007, 1-14). The flexibility of this method allows the synthesis of a large number of different compounds using a range of alkynes for the Sonogashira coupling, or by starting with a different amine for the amide formation in the first step. However, the main drawback of this synthetic route is that the Lindlar catalytic reduction of intermediate (S4) yields a mixture of E- and Z-isomers of the resulting alkenyl compounds, requiring separation by reverse phase HPLC. This technique is both costly and time consuming, thereby rendering the method unsuitable for large scale synthesis.
The present invention seeks to provide an alternative process for preparing VSN-16 and related compounds. More specifically—although not exclusively—the invention seeks to provide an improved process to those previously described in the art, and/or a process that is suitable for scale-up.